Increased C4d in post-reperfusion biopsies and increased donor specific antibodies at one-week post transplant are risk factors for acute rejection in mild to moderately sensitized kidney transplant recipients.

In order to define the intensity of immunosuppression, we examined risk factors for acute rejection in desensitization protocols that use baseline donor-specific antibody levels measured as mean fluorescence intensity (MFImax). The study included 146 patients transplanted with a negative flow crossmatch and a mean follow-up of 18 months with the majority (83%) followed for at least 1 year. At the time of transplant, mean-calculated panel-reactive antibody and MFImax ranged from 10.3-57.2% and 262-1691, respectively, between low- and high-risk protocols. Mean MFImax increased significantly from transplant to 1 week and 1 year. The incidence of acute rejection (mean 1.65 months) as a combination of clinical and subclinical rejection was 32%, including 14% cellular, 12% antibody-mediated, and 6% mixed rejection. In regression analyses, only C4d staining in post-reperfusion biopsies (hazard ratio 3.3, confidence interval 1.71-6.45) and increased specific antibodies at 1-week post transplant were significant predictors of rejection. A rise in MFImax by 500 was associated with a 2.8-fold risk of rejection. Thus, C4d staining in post-reperfusion biopsies and an early rise in donor specific antibodies after transplantation are risk factors for rejection in moderately sensitized patients.

Post-transplant DSA monitoring may predict antibody-mediated rejection in sensitized kidney transplant recipients.

We examined whether changes in posttransplant highest intensity donor specific anti-HLA antibody specificity (DSAmax) measured by single antigen bead via Luminex (One Lambda, Inc.) were associated with antibody-mediated rejection (AMR). We conducted a retrospective analysis examining risk factors for AMR in 116 consecutive patients who underwent desensitization between 1/1/2009 and 9/1/2010. All patients had a negative flow cytometry crossmatch. The mean patient age at transplant was 46.4 +/- 4 years. The mean peak PRA (panel reactive antibody) and DSAmax at transplant were 40 +/- 6% and 894 +/- 150 mean fluorescent intensity (MFI), respectively. The mean time to rejection was 1.5 +/- 0.4 months. Cox regression analyses demonstrated that an increase in DSAmax by one week after transplant was significantly associated with AMR (pure or mixed). A rise in DSAmax greater than 500 MFI at 1 week was associated with a 2.6 times greater risk of rejection (HR 2.6, 95% CI 1.1 - 6.3, p = 0.02). We conclude that a rise in DSAmax at one week is an independent risk factor forAMR and that posttransplant DSA monitoring strategies may reduce the risk of AMR in sensitized patients.